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Volume 26,Issue 7,2019 Table of Contents
2019, 26(7):725-729.
DOI: 10.3872/j.issn.1007-385X.2019.07.001
Abstract:
[Abstract] Gene-engineered T cells, represented by chimeric antigen receptor T cells (CAR-T cells), have achieved great success in hematological tumors, and gradually been applied in the clinical treatment of tumors. In 2017, two CD19-CAR products for hematological tumors were consecutively approved for marketing in America, and have shown powerful anti-tumor efficacy in non-solid tumor treatment.However, CAR-T cell therapy didn’t achieve expectant therapeutic efficacy in solid tumors due to complicated tumor microenvironment and restriction of surface tumor antigen. In addition, the cytotoxicity caused by off-target effects is more troublesome. To address these hurdles, more and more researchers have begun to explore new gene-edited T cells for solid tumor treatment, among which bispecific T cell engager T cell (BiTE T) has shown high anti-tumor efficacy in vitro evaluation and in vivo animal models and thus has attracted great attention. This review mainly discusses the current difficulties confronted by solid tumor treatment and the principles,characteristics and advantages of BiTE-T cell preparation.
[Abstract] Gene-engineered T cells, represented by chimeric antigen receptor T cells (CAR-T cells), have achieved great success in hematological tumors, and gradually been applied in the clinical treatment of tumors. In 2017, two CD19-CAR products for hematological tumors were consecutively approved for marketing in America, and have shown powerful anti-tumor efficacy in non-solid tumor treatment.However, CAR-T cell therapy didn’t achieve expectant therapeutic efficacy in solid tumors due to complicated tumor microenvironment and restriction of surface tumor antigen. In addition, the cytotoxicity caused by off-target effects is more troublesome. To address these hurdles, more and more researchers have begun to explore new gene-edited T cells for solid tumor treatment, among which bispecific T cell engager T cell (BiTE T) has shown high anti-tumor efficacy in vitro evaluation and in vivo animal models and thus has attracted great attention. This review mainly discusses the current difficulties confronted by solid tumor treatment and the principles,characteristics and advantages of BiTE-T cell preparation.
2019, 26(7):730-735.
DOI: 10.3872/j.issn.1007-385X.2019.07.002
Abstract:
[Abstract] Objective:To investigate the tumor-specific neoantigen for primary plasma cell leukemia (PCL) using gene sequencing technology combined with bioinformatic analysis. Methods: Peripheral blood samples of one patient with primary PCL during relapse and remission periods were collected. HLA molecular typing was performed using polymerase chain reaction with sequencing-based typing; whole-exome and transcriptome were sequenced by next-generation sequencing method; and bioinformatics software NetMHCpan was used to predict neoantigens. Results: Six tumor-specific missense mutations were found in the patient's peripheral blood during relapse period, located in genes FRG1, MLL3, SVIL, MYOM1, ZDHHC11 and RFPL4A.Considering patient's HLA sub-types, 43 neoantigens were predicted via bioinformatics. Considering that FRG1 and MLL3 had relatively high gene expression levels, 20 neoantigens derived from mutations of the two genes were preferentially selected, among which four neoantigens had high affinity with the patient's HLA molecules and thus had potential clinical application value. Conclusion: The study has completed a tumor neoantigen screen and prediction for primary PCL. This practice demonstrates that predicting neoantigen based on tumor-specific somatic mutation is feasible for primary PCL.
[Abstract] Objective:To investigate the tumor-specific neoantigen for primary plasma cell leukemia (PCL) using gene sequencing technology combined with bioinformatic analysis. Methods: Peripheral blood samples of one patient with primary PCL during relapse and remission periods were collected. HLA molecular typing was performed using polymerase chain reaction with sequencing-based typing; whole-exome and transcriptome were sequenced by next-generation sequencing method; and bioinformatics software NetMHCpan was used to predict neoantigens. Results: Six tumor-specific missense mutations were found in the patient's peripheral blood during relapse period, located in genes FRG1, MLL3, SVIL, MYOM1, ZDHHC11 and RFPL4A.Considering patient's HLA sub-types, 43 neoantigens were predicted via bioinformatics. Considering that FRG1 and MLL3 had relatively high gene expression levels, 20 neoantigens derived from mutations of the two genes were preferentially selected, among which four neoantigens had high affinity with the patient's HLA molecules and thus had potential clinical application value. Conclusion: The study has completed a tumor neoantigen screen and prediction for primary PCL. This practice demonstrates that predicting neoantigen based on tumor-specific somatic mutation is feasible for primary PCL.
2019, 26(7):736-742.
DOI: 10.3872/j.issn.1007-385X.2019.07.003
Abstract:
[Abstract] Objective: To investigate the correlation between the expression of E2F1 and growth arrest and DNA damage inducible protein 45g (GADD45g) in patients with acute myeloid leukemia (AML), and to explore whether GADD45g exerts its induction of DNA damage, cell apoptosis, senescence, cell cycle arrest and drug sensitivity in AML through inhibition of E2F1. Methods: A total of 32 cases of bone marrow specimens from patients initially diagnosed as AML in Hospital of Blood Diseases Affiliated to Chinese Academy of Medical Sciences from January 2013 to December 2016, were selected for this study; In addition, AML cell lines (U937, HL60,THP-1, Molm-13) were also collected for this study. The mRNA expression of GADD45g and E2F1 in above mentioned specimens and cell lines by qPCR, and their correlation was also analyzed. The lentiviral vector over-expressing E2F1 (pLV-E2F1-RFP) was constructed to prepare recombinant lentivirus, which was then transfected Molm-13 and THP-1 cells that over-expressing GADD45g. Whether GADD45g exerts tumor inhibition effect on AML cells through inhibition of E2F1 was determined by comet assay, Annexin V/7AAD flow cytometry, β-galactosidase staining and PI staining flow cytometry etc. Results: The mRNA expression of GADD45g was negatively correlated with E2F1 in bone marrow of AML patients and AML cell lines (r=–0.663, P<0.01). Over-expression of GADD45g significantly inhibited the expression of E2F1 in AML cell lines (all P<0.01). Molm-13 and THP-1 cells that simultaneously over-expressing GADD45g and E2F1 were successfully constructed. Compared with the control group, the protein expressions of GADD45g and E2F1 in over-expression groups were significantly increased (all P<0.01). Compared with cells over-expressing GADD45g alone,simultaneous over-expression of both GADD45g and E2F1 significantly reduced the apoptosis, senescence and DNA damage (all P<0.01), and rescued cell cycle arrest in Molm-13 and THP-1 cells (all P<0.01), thus further reduced the chemo-sensitivity of AML cells caused by GADD45g over-expression (all P<0.01). Conclusion: GADD45g exerts anti-tumor effect in AML via inhibition of E2F1.
[Abstract] Objective: To investigate the correlation between the expression of E2F1 and growth arrest and DNA damage inducible protein 45g (GADD45g) in patients with acute myeloid leukemia (AML), and to explore whether GADD45g exerts its induction of DNA damage, cell apoptosis, senescence, cell cycle arrest and drug sensitivity in AML through inhibition of E2F1. Methods: A total of 32 cases of bone marrow specimens from patients initially diagnosed as AML in Hospital of Blood Diseases Affiliated to Chinese Academy of Medical Sciences from January 2013 to December 2016, were selected for this study; In addition, AML cell lines (U937, HL60,THP-1, Molm-13) were also collected for this study. The mRNA expression of GADD45g and E2F1 in above mentioned specimens and cell lines by qPCR, and their correlation was also analyzed. The lentiviral vector over-expressing E2F1 (pLV-E2F1-RFP) was constructed to prepare recombinant lentivirus, which was then transfected Molm-13 and THP-1 cells that over-expressing GADD45g. Whether GADD45g exerts tumor inhibition effect on AML cells through inhibition of E2F1 was determined by comet assay, Annexin V/7AAD flow cytometry, β-galactosidase staining and PI staining flow cytometry etc. Results: The mRNA expression of GADD45g was negatively correlated with E2F1 in bone marrow of AML patients and AML cell lines (r=–0.663, P<0.01). Over-expression of GADD45g significantly inhibited the expression of E2F1 in AML cell lines (all P<0.01). Molm-13 and THP-1 cells that simultaneously over-expressing GADD45g and E2F1 were successfully constructed. Compared with the control group, the protein expressions of GADD45g and E2F1 in over-expression groups were significantly increased (all P<0.01). Compared with cells over-expressing GADD45g alone,simultaneous over-expression of both GADD45g and E2F1 significantly reduced the apoptosis, senescence and DNA damage (all P<0.01), and rescued cell cycle arrest in Molm-13 and THP-1 cells (all P<0.01), thus further reduced the chemo-sensitivity of AML cells caused by GADD45g over-expression (all P<0.01). Conclusion: GADD45g exerts anti-tumor effect in AML via inhibition of E2F1.
2019, 26(7):743-750.
DOI: 10.3872/j.issn.1007-385X.2019.07.004
Abstract:
[Abstract] Objective: To study the regulatory effects and possible mechanism of long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) on chemotherapy sensitivity to cisplatin (DDP) of colorectal cancer (CRC)．Methods: A total of 112 pairs of matched cancer and adjacent non-cancerous tissues were obtained from the CRC patients who underwent surgical resection in the First Affiliated Hospital of Xinxiang Medical University between April 2006 and March 2011. All specimens were confirmed by pathological examinations. Tumor tissues and corresponding adjacent non-cancerous tissues from 30 cisplatin-sensitive CRC patients and 30 cisplatin-resistant patients were selected. Human CRC cell lines (HT29, SW480, HCT116, RKO and LoVo) and normal colonic epithelial cell line NCM460 were also collected for this study; and DDP-resistant RKO/DDP and LoVo/DDP cell lines were constructed. siPVT1,siNC, LV-PVT1 and LV-NC were transfected into LoVo and RKO cells or LoVo/DDP and RKO/DDP cells using lipofectamineTM2000.The expression of lncRNA PVT1 in CRC tissues and cells was tested by Real-time qPCR. CCK-8 assay, flow cytometry and WB were performed to test the effect of PTV1 knockout or enforcement on cell proliferation, apoptosis and expressions of apoptosis-related roteins,respectively. The CRC subcutaneous transplanted xenograft model was established on athymic nude mice to study the effect of PVT1 over-expression on tumor growth and DDP resistance. Results: PVT1 was highly expressed in the cancer tissues and CRC cells,and its expression was positively associated with cisplatin resistance of CRC. After knockdown of PVT1, the proliferation of cisplatinresistant CRC cells was significantly suppressed, while the apoptosis was significantly enhanced (P<0.05 or P<0.01); Mechanically, the levels of drug resistance-associated molecules, including MDR1 and MRP1, as well as the expression of anti-apoptotic Bcl-2 were significantly downregulated whereas the levels of pro-apoptotic Bax and cleaved caspase-3 were increased in PVT1-silenced DDP-resistant CRC cells. Over-expression of PVT1 reversely increased proliferation and decreased apoptosis of CRC cells (P<0.05 or P<0.01).In addition, PVT1 over-expression in CRC cells significantly promoted DDP-resistance in vivo (P<0.05). Conclusion: Collectively,knockdown of PVT1 expression can significantly suppress cell proliferation and promote apoptosis of DDP-resistant CRC cells. Overexpression of PVT1 can significantly promote the growth of CRC cells in vitro and transplanted xenograft in vivo. PVT1 regulates endogenous apoptosis pathways and further promotes the sensitivity of CRC cells to cisplatin chemotherapy via inhibiting the expressions of MDR1 and MRP1.
[Abstract] Objective: To study the regulatory effects and possible mechanism of long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) on chemotherapy sensitivity to cisplatin (DDP) of colorectal cancer (CRC)．Methods: A total of 112 pairs of matched cancer and adjacent non-cancerous tissues were obtained from the CRC patients who underwent surgical resection in the First Affiliated Hospital of Xinxiang Medical University between April 2006 and March 2011. All specimens were confirmed by pathological examinations. Tumor tissues and corresponding adjacent non-cancerous tissues from 30 cisplatin-sensitive CRC patients and 30 cisplatin-resistant patients were selected. Human CRC cell lines (HT29, SW480, HCT116, RKO and LoVo) and normal colonic epithelial cell line NCM460 were also collected for this study; and DDP-resistant RKO/DDP and LoVo/DDP cell lines were constructed. siPVT1,siNC, LV-PVT1 and LV-NC were transfected into LoVo and RKO cells or LoVo/DDP and RKO/DDP cells using lipofectamineTM2000.The expression of lncRNA PVT1 in CRC tissues and cells was tested by Real-time qPCR. CCK-8 assay, flow cytometry and WB were performed to test the effect of PTV1 knockout or enforcement on cell proliferation, apoptosis and expressions of apoptosis-related roteins,respectively. The CRC subcutaneous transplanted xenograft model was established on athymic nude mice to study the effect of PVT1 over-expression on tumor growth and DDP resistance. Results: PVT1 was highly expressed in the cancer tissues and CRC cells,and its expression was positively associated with cisplatin resistance of CRC. After knockdown of PVT1, the proliferation of cisplatinresistant CRC cells was significantly suppressed, while the apoptosis was significantly enhanced (P<0.05 or P<0.01); Mechanically, the levels of drug resistance-associated molecules, including MDR1 and MRP1, as well as the expression of anti-apoptotic Bcl-2 were significantly downregulated whereas the levels of pro-apoptotic Bax and cleaved caspase-3 were increased in PVT1-silenced DDP-resistant CRC cells. Over-expression of PVT1 reversely increased proliferation and decreased apoptosis of CRC cells (P<0.05 or P<0.01).In addition, PVT1 over-expression in CRC cells significantly promoted DDP-resistance in vivo (P<0.05). Conclusion: Collectively,knockdown of PVT1 expression can significantly suppress cell proliferation and promote apoptosis of DDP-resistant CRC cells. Overexpression of PVT1 can significantly promote the growth of CRC cells in vitro and transplanted xenograft in vivo. PVT1 regulates endogenous apoptosis pathways and further promotes the sensitivity of CRC cells to cisplatin chemotherapy via inhibiting the expressions of MDR1 and MRP1.
2019, 26(7):751-756.
DOI: 10.3872/j.issn.1007-385X.2019.07.005
Abstract:
[Abstract] Objective: To investigate the expression of lncRNA LINC00886 in human esophageal squamous cell carcinoma (ESCC) tissues and cell lines, and its effects on proliferation, migration and invasion of Eca109 cells. Methods: The cancer tissues and corresponding para-cancerous tissues of 69 ESCC patients were collected in the biological specimen bank of the Fourth Hospital of Hebei Medical University from June 2014 to December 2016; the ESCC cell lines Eca109, TE13, TE1, Kyse150, Yes-2 and Kyse170 were also collected. LINC00886 gene expression in ESCC tissues and cell lines was detected by qPCR. Eca109 cells were transfected with pIRES2-LINC00886 and pIRES2-NC, respectively, and the overexpression efficiency of LINC00886 gene in Eca109 cells was detected by qPCR; MTS, clone formation assay, wound-healing assay and Transwell invasion assay were respectively used to detect the effect of LINC00886 over-expression on proliferation, migration and invasion ability of Eca109 cells. Results: The expression of LINC00886 gene in ESCC tissues was significantly lower than that in para-cancerous tissues (P<0.01), and its expression level was associated with tumor TNM stage and lymph node metastasis (both P<0.05). The expression level of LINC00886 gene in ESCC cell lines was also lower than that of the control group (all P<0.01). Compared with control group, the expression level of LINC00886 gene was significantly higher in Eca109 cells transfected with pIRES2-LINC00886 (both P<0.05). Compared with the control group, LINC00886 overexpression significantly inhibited the proliferation, migration and invasion abilities of Eca109 cells (all P<0.01). Conclusion: The decreased expression of LINC00886 gene may be related to the occurrence and development of ESCC. Over-expression of LINC00886 gene inhibits the proliferation, migration and invasion abilities of ESCC cells.
[Abstract] Objective: To investigate the expression of lncRNA LINC00886 in human esophageal squamous cell carcinoma (ESCC) tissues and cell lines, and its effects on proliferation, migration and invasion of Eca109 cells. Methods: The cancer tissues and corresponding para-cancerous tissues of 69 ESCC patients were collected in the biological specimen bank of the Fourth Hospital of Hebei Medical University from June 2014 to December 2016; the ESCC cell lines Eca109, TE13, TE1, Kyse150, Yes-2 and Kyse170 were also collected. LINC00886 gene expression in ESCC tissues and cell lines was detected by qPCR. Eca109 cells were transfected with pIRES2-LINC00886 and pIRES2-NC, respectively, and the overexpression efficiency of LINC00886 gene in Eca109 cells was detected by qPCR; MTS, clone formation assay, wound-healing assay and Transwell invasion assay were respectively used to detect the effect of LINC00886 over-expression on proliferation, migration and invasion ability of Eca109 cells. Results: The expression of LINC00886 gene in ESCC tissues was significantly lower than that in para-cancerous tissues (P<0.01), and its expression level was associated with tumor TNM stage and lymph node metastasis (both P<0.05). The expression level of LINC00886 gene in ESCC cell lines was also lower than that of the control group (all P<0.01). Compared with control group, the expression level of LINC00886 gene was significantly higher in Eca109 cells transfected with pIRES2-LINC00886 (both P<0.05). Compared with the control group, LINC00886 overexpression significantly inhibited the proliferation, migration and invasion abilities of Eca109 cells (all P<0.01). Conclusion: The decreased expression of LINC00886 gene may be related to the occurrence and development of ESCC. Over-expression of LINC00886 gene inhibits the proliferation, migration and invasion abilities of ESCC cells.
2019, 26(7):757-761.
DOI: 10.3872/j.issn.1007-385X.2019.07.006
Abstract:
[Abstract] Objective: To investigate the effect of human epididymal protein 4 (HE4) and paired box gene 8 (PAX8) gene knockdown on proliferation, migration, invasion and apoptosis of human epithelial ovarian cancer OVCAR3 cells treated with TC regimen (paclitaxel+carboplatin). Methods: Sequences of single-target siRNA (HE4-siRNA or PAX8-siRNA) and double-target siRNA (HE4+PAX8-siRNA) as well as negative siRNA were respectively designed and synthesized, and then linked with plasmid vector pGCsi-H1 to obtain the recombinant plasmids. The obtained recombinant plasmids were then transfected into human epithelial ovarian cancer OVCAR3 cells, namely HE4-siRNA group, PAX8-siRNA group, HE4+PAX8-siRNA group and siRNA-NC group, respectively. The blank control group was also set up (without any treatment). The cells in above five groups were treated with TC regimen (paclitaxel 3.13 g/ml+carboplatin 2.82 μg/ml), and the changes in proliferation, migration, invasion and apoptosis of the cells were detected by MTT, wound-healing assay, Transwell chamber assay, and flow cytometry, respectively. Results: After knocking down the HE4 and PAX8 genes, compared with siRNA-NC group and blank control group, the proliferation, migration and invasion abilities of OVCAR3 cells in HE4-siRNA group, PAX8-siRNA group and HE4+PAX8-siRNA group significantly decreased (all P<0.01), and the apoptosis rate significantly increased (P<0.01), especially in HE4+PAX8-siRNA group. Conclusion: Knockout of either HE4 or PAX8 can enhance the effect of TC regimen on inhibiting proliferation, migration and invasion as well as promoting apoptosis of epithelial ovarian cancer cells, and the effect of simultaneous down-regulation of HE4 together with PAX8 is better.
[Abstract] Objective: To investigate the effect of human epididymal protein 4 (HE4) and paired box gene 8 (PAX8) gene knockdown on proliferation, migration, invasion and apoptosis of human epithelial ovarian cancer OVCAR3 cells treated with TC regimen (paclitaxel+carboplatin). Methods: Sequences of single-target siRNA (HE4-siRNA or PAX8-siRNA) and double-target siRNA (HE4+PAX8-siRNA) as well as negative siRNA were respectively designed and synthesized, and then linked with plasmid vector pGCsi-H1 to obtain the recombinant plasmids. The obtained recombinant plasmids were then transfected into human epithelial ovarian cancer OVCAR3 cells, namely HE4-siRNA group, PAX8-siRNA group, HE4+PAX8-siRNA group and siRNA-NC group, respectively. The blank control group was also set up (without any treatment). The cells in above five groups were treated with TC regimen (paclitaxel 3.13 g/ml+carboplatin 2.82 μg/ml), and the changes in proliferation, migration, invasion and apoptosis of the cells were detected by MTT, wound-healing assay, Transwell chamber assay, and flow cytometry, respectively. Results: After knocking down the HE4 and PAX8 genes, compared with siRNA-NC group and blank control group, the proliferation, migration and invasion abilities of OVCAR3 cells in HE4-siRNA group, PAX8-siRNA group and HE4+PAX8-siRNA group significantly decreased (all P<0.01), and the apoptosis rate significantly increased (P<0.01), especially in HE4+PAX8-siRNA group. Conclusion: Knockout of either HE4 or PAX8 can enhance the effect of TC regimen on inhibiting proliferation, migration and invasion as well as promoting apoptosis of epithelial ovarian cancer cells, and the effect of simultaneous down-regulation of HE4 together with PAX8 is better.
7 miR-137 inhibits proliferation, invasion and migration of cervical cancer cells by targeting Wnt5a
2019, 26(7):762-767.
DOI: 10.3872/j.issn.1007-385X.2019.07.007
Abstract:
[Abstract] Objective：To investigate the expression of miR-137 in cervical cancer tissues and cells, and to explore its effect on proliferation,migration and invasion of cervical cancer cells as well as the mechanisms. Methods：Thirty-two pairs of cervical cancer tissues and corresponding para-cancerous tissues that surgically resected at the Department of Gynecology and Obstetrics of Dongguan People's Hospital from January 2017 to March 2018 were collected for this study. In addition, cervical cancer cell lines C33A, HeLa, SiHa and cervical epithelial immortalized cell line H8 were also collected. The expression of miR-137 in cervical cancer tissues and cell lines was detected by RT-PCR. miR-137 mimics and miR-137 NC were respectively transfected into C33A and HeLa cells, and the effects of miR-137 over-expression on proliferation, migration and invasion of cervical cancer cell lines were observed by CCK-8 and Transwell assay. Luciferase reporter gene assay and WB were used to determine the relationship between miR-137 and Wnt5a in cervical cancer.Wnt5a over-expression vector was constructed, and the effects of simultaneous over-expression of Wnt5a and miR-137 on proliferation,migration and invasion of C33A and HeLa cells were observed. Results：The expression level of miR-137 was significantly down-regulated in cervical cancer tissues and cell lines, as compared to para-cancerous tissues and H8 cells (all P<0.05). The over-expression of miR-137 significantly inhibited cell proliferation, migration and invasion of C33A and HeLa cells (all P<0.05). Moreover, Wnt5a was identified as a target of miR-137 by luciferase reporter gene assay. Furthermore, Wnt5a over-expression, to a certain degree, attenuated the suppressive effects of miR-137 on the proliferation, migration and invasion of C33A and HeLa cells. Conclusion：miR-137 can inhibit the proliferation, migration and invasion of cervical cancer cells via targeting Wnt5a, which may be an effective target for the treatment of cervical cancer.
[Abstract] Objective：To investigate the expression of miR-137 in cervical cancer tissues and cells, and to explore its effect on proliferation,migration and invasion of cervical cancer cells as well as the mechanisms. Methods：Thirty-two pairs of cervical cancer tissues and corresponding para-cancerous tissues that surgically resected at the Department of Gynecology and Obstetrics of Dongguan People's Hospital from January 2017 to March 2018 were collected for this study. In addition, cervical cancer cell lines C33A, HeLa, SiHa and cervical epithelial immortalized cell line H8 were also collected. The expression of miR-137 in cervical cancer tissues and cell lines was detected by RT-PCR. miR-137 mimics and miR-137 NC were respectively transfected into C33A and HeLa cells, and the effects of miR-137 over-expression on proliferation, migration and invasion of cervical cancer cell lines were observed by CCK-8 and Transwell assay. Luciferase reporter gene assay and WB were used to determine the relationship between miR-137 and Wnt5a in cervical cancer.Wnt5a over-expression vector was constructed, and the effects of simultaneous over-expression of Wnt5a and miR-137 on proliferation,migration and invasion of C33A and HeLa cells were observed. Results：The expression level of miR-137 was significantly down-regulated in cervical cancer tissues and cell lines, as compared to para-cancerous tissues and H8 cells (all P<0.05). The over-expression of miR-137 significantly inhibited cell proliferation, migration and invasion of C33A and HeLa cells (all P<0.05). Moreover, Wnt5a was identified as a target of miR-137 by luciferase reporter gene assay. Furthermore, Wnt5a over-expression, to a certain degree, attenuated the suppressive effects of miR-137 on the proliferation, migration and invasion of C33A and HeLa cells. Conclusion：miR-137 can inhibit the proliferation, migration and invasion of cervical cancer cells via targeting Wnt5a, which may be an effective target for the treatment of cervical cancer.
WEN Chunmeia
,
LI Zixuana
,
WANG Yua
,
ZHU Xuejun
,
MENG Huimina
,
JU Jiea
,
ZHANG Tingtinga
,
ZHANG Xiuyana
,
YUANLei
,
AN Ganglia
,
YANG Lina
,
b
,
c
,
2019, 26(7):768-775.
DOI: 10.3872/j.issn.1007-385X.2019.07.008
Abstract:
[Abstract] Objective: To investigate the expression and clinical significance of PD-1 molecule in tumor cells (T-ALL cells) derived from the patient with T-cell acute lymphoblastic leukemia (T-ALL). Methods: T-ALL cells from one patient and PBMCs from four healthy volunteers provided by the Department of Hematology in Jiangsu Provincial Hospital of Traditional Chinese Medicine in December 2015, and human 293T/PD-1 cells provided by Persongen Bio Therapeutics (Suzhou) Co., Ltd. were used for this study. The mouse T-ALL xenograft model was constructed by injecting T-ALL cells into tail vein of B-NDG mice, and flow cytometry was used to verify whether the cells obtained from the spleen of transplanted mice were mainly consisted of T-ALL cells. Flow cytometry was used to study the protein expression of PD-1 in T-ALL cells, and RT-PCR was applied to further verify the mRNA expression of PD-1 in T-ALL cells. The PD-1 gene in T-ALL cells was sequenced by SNP genotyping to detect whether the DNA sequence of PD-1 gene changed. PD-1 inhibitor was used in vitro to study their effects on proliferation, apoptosis, and the mRNA expression levels of related factors in T-ALL cells. Results: The mouse T-ALL xenograft model was successfully constructed and verified by flow cytometry as T-ALL. PD-1 was highly expressed at both mRNA and protein levels in T-ALL cells (all P<0.01). A C-to-T mutation was detected in the fifth exon of the PD-1 gene. PD-1 inhibitor had no significant effect on proliferation and apoptosis of T-ALL cells in vitro; PD-1 inhibitor up-regulated the mRNA expression of tumor-suppressor protein IGFBP3 and decreased the mRNA expression of oncoprotein SULT1A3 (all P<0.01). Conclusion: PD-1 is highly expressed in T-ALL cells, and PD-1 could be used as a target for clinical diagnosis and treatment for T-ALL.
[Abstract] Objective: To investigate the expression and clinical significance of PD-1 molecule in tumor cells (T-ALL cells) derived from the patient with T-cell acute lymphoblastic leukemia (T-ALL). Methods: T-ALL cells from one patient and PBMCs from four healthy volunteers provided by the Department of Hematology in Jiangsu Provincial Hospital of Traditional Chinese Medicine in December 2015, and human 293T/PD-1 cells provided by Persongen Bio Therapeutics (Suzhou) Co., Ltd. were used for this study. The mouse T-ALL xenograft model was constructed by injecting T-ALL cells into tail vein of B-NDG mice, and flow cytometry was used to verify whether the cells obtained from the spleen of transplanted mice were mainly consisted of T-ALL cells. Flow cytometry was used to study the protein expression of PD-1 in T-ALL cells, and RT-PCR was applied to further verify the mRNA expression of PD-1 in T-ALL cells. The PD-1 gene in T-ALL cells was sequenced by SNP genotyping to detect whether the DNA sequence of PD-1 gene changed. PD-1 inhibitor was used in vitro to study their effects on proliferation, apoptosis, and the mRNA expression levels of related factors in T-ALL cells. Results: The mouse T-ALL xenograft model was successfully constructed and verified by flow cytometry as T-ALL. PD-1 was highly expressed at both mRNA and protein levels in T-ALL cells (all P<0.01). A C-to-T mutation was detected in the fifth exon of the PD-1 gene. PD-1 inhibitor had no significant effect on proliferation and apoptosis of T-ALL cells in vitro; PD-1 inhibitor up-regulated the mRNA expression of tumor-suppressor protein IGFBP3 and decreased the mRNA expression of oncoprotein SULT1A3 (all P<0.01). Conclusion: PD-1 is highly expressed in T-ALL cells, and PD-1 could be used as a target for clinical diagnosis and treatment for T-ALL.
2019, 26(7):776-781.
DOI: 10.3872/j.issn.1007-385X.2019.07.009
Abstract:
[Abstract] Objective: To discuss the relationship between lymph node metastasis rate and the prognosis of patients with stage II and III breast cancer with different molecular subtypes. Methods: The clinical data of 311 patients diagnosed with stage II and III breast cancer, who received preferred surgical treatment in Changzhou Second People's Hospital Affiliated to Nanjing Medical University from January 2011 to January 2016, were retrospectively analyzed. According to the levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2) and Ki-67 proliferation index, the patients were divided into four groups, namely,Luminal A, Luminal B, HER2 over-expression and triple negative breast cancer (TNBC). Chi-square test was used to analyze the clinical characteristics of patients in different groups. Kaplan-Meier survival curve was used to evaluate the prognostic impact of axillary lymph node metastasis rate (LNR) on patients with different types of breast cancer, and the prognostic differences among breast cancer patients with different molecular subtypes under the same LNR. Spearman correlation was used to analyze the correlation between LNR and Ki-67 proliferation index. Results: There were no significant differences in clinical characteristics of age, menopause,tumor size, lymph node status and metastasis site among BC patients with different molecular subtypes (all P>0.05). There was no significant difference in disease-free survival (DFS) among the four subgroups with LNR of 0 or >0.65 (χ2=3.581, 2.808, all P>0.05); and there was significant difference in DFS among the four subgroups with LNR between 0.01 and 0.65 (χ2=24.366, 8.169, all P<0.05).LNR was positively correlated with the Ki-67 proliferation index (r=0.125, P<0.05). Multivariate Cox regression analysis showed that the prognosis of breast cancer patients was related to molecular subtypes (RR=1.179, 95%CI=1.023-1.358; χ2=5.165, P<0.05), LNR (RR =1.137, 95%CI=0.985-0.999; χ2=5.589, P<0.05) and Ki-67 proliferation index (RR=0.992, 95%CI=1.022-1.264; χ2=5.623，P<0.05).Conclusion: LNR is an important prognostic factor for stage II and III breast cancer. With the same LNR, the prognosis of breast cancer patients with different molecular subtypes varies greatly. LNR is positively correlated with Ki-67 proliferation index.
[Abstract] Objective: To discuss the relationship between lymph node metastasis rate and the prognosis of patients with stage II and III breast cancer with different molecular subtypes. Methods: The clinical data of 311 patients diagnosed with stage II and III breast cancer, who received preferred surgical treatment in Changzhou Second People's Hospital Affiliated to Nanjing Medical University from January 2011 to January 2016, were retrospectively analyzed. According to the levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2) and Ki-67 proliferation index, the patients were divided into four groups, namely,Luminal A, Luminal B, HER2 over-expression and triple negative breast cancer (TNBC). Chi-square test was used to analyze the clinical characteristics of patients in different groups. Kaplan-Meier survival curve was used to evaluate the prognostic impact of axillary lymph node metastasis rate (LNR) on patients with different types of breast cancer, and the prognostic differences among breast cancer patients with different molecular subtypes under the same LNR. Spearman correlation was used to analyze the correlation between LNR and Ki-67 proliferation index. Results: There were no significant differences in clinical characteristics of age, menopause,tumor size, lymph node status and metastasis site among BC patients with different molecular subtypes (all P>0.05). There was no significant difference in disease-free survival (DFS) among the four subgroups with LNR of 0 or >0.65 (χ2=3.581, 2.808, all P>0.05); and there was significant difference in DFS among the four subgroups with LNR between 0.01 and 0.65 (χ2=24.366, 8.169, all P<0.05).LNR was positively correlated with the Ki-67 proliferation index (r=0.125, P<0.05). Multivariate Cox regression analysis showed that the prognosis of breast cancer patients was related to molecular subtypes (RR=1.179, 95%CI=1.023-1.358; χ2=5.165, P<0.05), LNR (RR =1.137, 95%CI=0.985-0.999; χ2=5.589, P<0.05) and Ki-67 proliferation index (RR=0.992, 95%CI=1.022-1.264; χ2=5.623，P<0.05).Conclusion: LNR is an important prognostic factor for stage II and III breast cancer. With the same LNR, the prognosis of breast cancer patients with different molecular subtypes varies greatly. LNR is positively correlated with Ki-67 proliferation index.
2019, 26(7):782-787.
DOI: 10.3872/j.issn.1007-385X.2019.07.010
Abstract:
[Abstract] Objective: To investigate the expressions of chemokine-like factor superfamily 6 (CMTM6) and programmed cell death ligand 1 (PD-L1) in glioma tissues and their correlation with clinicopathological features of patients. Methods：From January 2012 to December 2015, 86 brain glioma tissues and 30 brain tissues (Control group) from patients operated with decompressive of craniotomy were collected from the Fifth Affiliated Hospital of Zhengzhou University. The distribution and expressions of CMTM6 and PD-L1 protein in brain glioma tissues were detected by immunohistochemistry and WB methods. The differential expression of CMTM6 and PDL1 between glioma tissues and normal brain tissues was analyzed by t test of two independent samples. Single variant χ2 test was used to analyze the relationship between the expression of CMTM6, PD-L1 and the clinicopathological features of patients. Results: The expression of CMTM6 in glioma tissues was significantly higher than that in control tissues (P<0.01). The expression levels of CMTM6 and PD-L1 in high pathological grade (WHO III-IV) glioma tissues were significantly higher than those in low pathological grade (WHO I-II) glioma tissues (all P<0.01). The expression of CMTM6 was correlated with pathological grade, dizziness history, epilepsy seizure and PD-L1 expression (all P<0.05), while the expression of PD-L1 was correlated with pathological grade, epilepsy seizure and CMTM6 expression (all P<0.05). Conclusion: There is a correlation between the expression of CMTM6 and PD-L1 in glioma tissues,both of which are highly expressed and are expected to be used to study glioma signaling pathways.
[Abstract] Objective: To investigate the expressions of chemokine-like factor superfamily 6 (CMTM6) and programmed cell death ligand 1 (PD-L1) in glioma tissues and their correlation with clinicopathological features of patients. Methods：From January 2012 to December 2015, 86 brain glioma tissues and 30 brain tissues (Control group) from patients operated with decompressive of craniotomy were collected from the Fifth Affiliated Hospital of Zhengzhou University. The distribution and expressions of CMTM6 and PD-L1 protein in brain glioma tissues were detected by immunohistochemistry and WB methods. The differential expression of CMTM6 and PDL1 between glioma tissues and normal brain tissues was analyzed by t test of two independent samples. Single variant χ2 test was used to analyze the relationship between the expression of CMTM6, PD-L1 and the clinicopathological features of patients. Results: The expression of CMTM6 in glioma tissues was significantly higher than that in control tissues (P<0.01). The expression levels of CMTM6 and PD-L1 in high pathological grade (WHO III-IV) glioma tissues were significantly higher than those in low pathological grade (WHO I-II) glioma tissues (all P<0.01). The expression of CMTM6 was correlated with pathological grade, dizziness history, epilepsy seizure and PD-L1 expression (all P<0.05), while the expression of PD-L1 was correlated with pathological grade, epilepsy seizure and CMTM6 expression (all P<0.05). Conclusion: There is a correlation between the expression of CMTM6 and PD-L1 in glioma tissues,both of which are highly expressed and are expected to be used to study glioma signaling pathways.
KONG Lianguang
,
PENG Junling
,
ZHENG Xiangzhen
,
SU Fang
,
WEI Yishenga
,
ZHANG Xiaoa
,
HONG Chuyuana
,
WENG Jielingb
2019, 26(7):788-792.
DOI: 10.3872/j.issn.1007-385X.2019.07.011
Abstract:
[Abstract] Objective: To explore the association between single nucleotide polymorphism rs12632942 in SCN10A exon and oxaliplatin-induced peripheral neuropathy (OXLIPN) in colorectal cancer (CRC) patients receiving chemotherapy. Methods:A total of 319 cases of blood samples from CRC patients receiving chemotherapy regimen with Oxaliplatin (OXL) were collected from the Second Affiliated Hospital of Guangzhou Medical University, the Second Affiliated Hospital of Nanchang University, and Guangzhou Baiyun District Hospital of Chinese Medicine during January 2011 and June 2013. DNA was routinely extracted, and PCR amplification was performed to analyze the genotype of rs12632942; and OXLIPN of patients was also evaluated. The association between rs12632942 genotype and OXLIPN was analyzed by χ2 test and multivariate logistic regression model. Results: The genotypes of rs12632942 of 319 CRC patients:AA of 134 cases, AG of 156 cases and GG of 29 cases; and the genotype distribution of rs12632942 was in accordance with Har-dy-Weinberg equiliberum (P>0.05). χ 2 test showed that rs12632942AG+GG genotype was associated with Ⅱ-Ⅳ degree OXLIPN (P<0.01). Multivariate logistic regression model showed that rs12632942 AG + GG genotype was an independent risk factor for Ⅱ-Ⅳ degree OXLIPN（OR=2.044；95%CI=1.231-3.392; P<0.01）. Conclusion: Colorectal cancer patients with SCN10A exon polymorphism rs12632942 AG + GG genotype were susceptible to Ⅱ-Ⅳ degree OXLIPN.
[Abstract] Objective: To explore the association between single nucleotide polymorphism rs12632942 in SCN10A exon and oxaliplatin-induced peripheral neuropathy (OXLIPN) in colorectal cancer (CRC) patients receiving chemotherapy. Methods:A total of 319 cases of blood samples from CRC patients receiving chemotherapy regimen with Oxaliplatin (OXL) were collected from the Second Affiliated Hospital of Guangzhou Medical University, the Second Affiliated Hospital of Nanchang University, and Guangzhou Baiyun District Hospital of Chinese Medicine during January 2011 and June 2013. DNA was routinely extracted, and PCR amplification was performed to analyze the genotype of rs12632942; and OXLIPN of patients was also evaluated. The association between rs12632942 genotype and OXLIPN was analyzed by χ2 test and multivariate logistic regression model. Results: The genotypes of rs12632942 of 319 CRC patients:AA of 134 cases, AG of 156 cases and GG of 29 cases; and the genotype distribution of rs12632942 was in accordance with Har-dy-Weinberg equiliberum (P>0.05). χ 2 test showed that rs12632942AG+GG genotype was associated with Ⅱ-Ⅳ degree OXLIPN (P<0.01). Multivariate logistic regression model showed that rs12632942 AG + GG genotype was an independent risk factor for Ⅱ-Ⅳ degree OXLIPN（OR=2.044；95%CI=1.231-3.392; P<0.01）. Conclusion: Colorectal cancer patients with SCN10A exon polymorphism rs12632942 AG + GG genotype were susceptible to Ⅱ-Ⅳ degree OXLIPN.
2019, 26(7):793-797.
DOI: 10.3872/j.issn.1007-385X.2019.07.012
Abstract:
[Abstract] Objective: To investigate the relationship between drug resistance and expression of ABC-binding cassette subfamily B member 1 (ABCB1) as well as its promoter methylation in pancreatic cancer. Methods: Fifteen pairs of pancreatic cancerous tissues and corresponding para-cancerous tissues, which were pathologically verified in Fujian Cancer Hospital from August 2015 to August 2018, were collected for this study; in addition, 3 cases of normal pancreatic tissues and pancreatic cancer cell line SW1990 were also collected. Gemcitabine (GEM)-resistant human pancreatic cancer cell line SW1990/GZ was induced by intermittent concentration gradient multiplication method. The expression level of ABCB1 in SW1990 cells, SW1990/GZ cells, pancreatic cancer tissues and apara-cancerous tissues was detected by qPCR. Methylation of ABCB1 promoter region in SW1990 cells, SW1990/GZ cells and pancreatic cancerous tissues was determined by MSP-PCR. Results: Compared with SW1990 cells, the morphology of SW1990/GZ cells showed more vacuoles, more mitotic images, clumpy growth and increased drug resistance (P<0.05). ABCB1 expression in pancreatic cancer tissues was significantly higher than that in para-cancerous tissues (P<0.01). The expression of ABCB1 in SW1990 and SW1990/GZ cells was significantly higher than that in normal pancreatic tissues (P<0.05 or P<0.01), and the expression of ABCB1 in SW1990/GZ cells was higher than that in SW1990 cells (P<0.05). ABCB1 promoters in SW1990, SW1990/GZ cells and normal pancreatic tissues were hypomethylated. Rate of methylation in pancreatic cancerous tissues and normal pancreatic tissues was 6.7%(1/15) and 0.00%(0/3) respectively, and the difference was statistically insignificant (all P>0.05). Conclusion: Increased ABCB1 expression in pancreatic cancer tissues and cells is associated with drug resistance, but its gene expression does not depend on promoter methylation regulation.
[Abstract] Objective: To investigate the relationship between drug resistance and expression of ABC-binding cassette subfamily B member 1 (ABCB1) as well as its promoter methylation in pancreatic cancer. Methods: Fifteen pairs of pancreatic cancerous tissues and corresponding para-cancerous tissues, which were pathologically verified in Fujian Cancer Hospital from August 2015 to August 2018, were collected for this study; in addition, 3 cases of normal pancreatic tissues and pancreatic cancer cell line SW1990 were also collected. Gemcitabine (GEM)-resistant human pancreatic cancer cell line SW1990/GZ was induced by intermittent concentration gradient multiplication method. The expression level of ABCB1 in SW1990 cells, SW1990/GZ cells, pancreatic cancer tissues and apara-cancerous tissues was detected by qPCR. Methylation of ABCB1 promoter region in SW1990 cells, SW1990/GZ cells and pancreatic cancerous tissues was determined by MSP-PCR. Results: Compared with SW1990 cells, the morphology of SW1990/GZ cells showed more vacuoles, more mitotic images, clumpy growth and increased drug resistance (P<0.05). ABCB1 expression in pancreatic cancer tissues was significantly higher than that in para-cancerous tissues (P<0.01). The expression of ABCB1 in SW1990 and SW1990/GZ cells was significantly higher than that in normal pancreatic tissues (P<0.05 or P<0.01), and the expression of ABCB1 in SW1990/GZ cells was higher than that in SW1990 cells (P<0.05). ABCB1 promoters in SW1990, SW1990/GZ cells and normal pancreatic tissues were hypomethylated. Rate of methylation in pancreatic cancerous tissues and normal pancreatic tissues was 6.7%(1/15) and 0.00%(0/3) respectively, and the difference was statistically insignificant (all P>0.05). Conclusion: Increased ABCB1 expression in pancreatic cancer tissues and cells is associated with drug resistance, but its gene expression does not depend on promoter methylation regulation.
2019, 26(7):798-801.
DOI: 10.3872/j.issn.1007-385X.2019.07.013
Abstract:
[摘要] 纳武单抗（nivolumab）为一全人源化IgG4 单克隆抗体靶向PD-1 免疫检查点抑制剂，主要通过克服患者体内的免疫抑制，重新激活免疫细胞来杀伤肿瘤细胞，是一种全新的抗肿瘤理念。纳武单抗作为抗PD-1 受体免疫检查点抑制剂，可通过封闭T 淋巴细胞的PD-1，阻断其与肿瘤细胞表面PD-L1 结合，解除肿瘤细胞对免疫细胞的抑制，使免疫细胞重新发挥抗肿瘤免疫作用而杀伤肿瘤细胞。纳武单抗于2015 年3 月被美国FDA 批准治疗铂基治疗进展后转移性鳞状非小细胞肺癌（NSCLC）。7 个月后，FDA在同样条件下批准该药物用于非鳞状NSCLC患者。本文主要介绍纳武单抗的药物作用机制、药效学、药动学、临床试验和安全性等的最新研究进展，为临床用药提供参考。
[摘要] 纳武单抗（nivolumab）为一全人源化IgG4 单克隆抗体靶向PD-1 免疫检查点抑制剂，主要通过克服患者体内的免疫抑制，重新激活免疫细胞来杀伤肿瘤细胞，是一种全新的抗肿瘤理念。纳武单抗作为抗PD-1 受体免疫检查点抑制剂，可通过封闭T 淋巴细胞的PD-1，阻断其与肿瘤细胞表面PD-L1 结合，解除肿瘤细胞对免疫细胞的抑制，使免疫细胞重新发挥抗肿瘤免疫作用而杀伤肿瘤细胞。纳武单抗于2015 年3 月被美国FDA 批准治疗铂基治疗进展后转移性鳞状非小细胞肺癌（NSCLC）。7 个月后，FDA在同样条件下批准该药物用于非鳞状NSCLC患者。本文主要介绍纳武单抗的药物作用机制、药效学、药动学、临床试验和安全性等的最新研究进展，为临床用药提供参考。
2019, 26(7):802-809.
DOI: 10.3872/j.issn.1007-385X.2019.07.014
Abstract:
[摘要] CAR-T细胞治疗血液肿瘤已经取得了不错的疗效，已有两款新药（Kymrial 和Yescata）上市。然而，在临床上CAR-T细胞疗法也面临诸如细胞因子释放综合征（CRS）、脱靶现象、载体安全性问题、实体瘤治疗效果不佳、肿瘤复发率高等问题，这使研究者们不得不重点关注其毒副作用的危害，并对此展开相关对策的研究。随着对CAR-T细胞认识的不断深入以及对治疗方案的不断优化，已经有部分毒副作用处于可控范围内。本文将对近年来CAR-T细胞治疗在临床应用中产生的问题进行分析，并介绍相应的对策，旨在为临床医生更好地管理CAR-T细胞治疗过程和肿瘤研究者进一步优化CAR结构提供参考依据。
[摘要] CAR-T细胞治疗血液肿瘤已经取得了不错的疗效，已有两款新药（Kymrial 和Yescata）上市。然而，在临床上CAR-T细胞疗法也面临诸如细胞因子释放综合征（CRS）、脱靶现象、载体安全性问题、实体瘤治疗效果不佳、肿瘤复发率高等问题，这使研究者们不得不重点关注其毒副作用的危害，并对此展开相关对策的研究。随着对CAR-T细胞认识的不断深入以及对治疗方案的不断优化，已经有部分毒副作用处于可控范围内。本文将对近年来CAR-T细胞治疗在临床应用中产生的问题进行分析，并介绍相应的对策，旨在为临床医生更好地管理CAR-T细胞治疗过程和肿瘤研究者进一步优化CAR结构提供参考依据。
2019, 26(7):810-816.
DOI: 10.3872/j.issn.1007-385X.2019.07.015
Abstract:
[摘要] 近年来研究显示，肠道菌群不仅与肿瘤的发生、发展和转移有关，还可通过参与化疗药物代谢导致化疗相关性肠炎、激活或调控免疫反应及信号通路、促进细胞因子的产生、修复肠道黏膜损伤等多种途径影响肿瘤患者对化疗、放疗和生物治疗的疗效和不良反应。肠道菌群种类繁多、丰度可变，个体差异性是患者对抗肿瘤治疗产生不同反应的原因之一。而肠道菌群受不同外源性因素的影响，故对其干预或重塑将增强抗肿瘤治疗的疗效和减轻治疗相关的毒副作用，改善肿瘤患者的生活质量和预后。本文就肠道菌群对化疗、放疗和免疫治疗的调控作用及相关机制，就靶向肠道菌群的治疗以提高抗肿瘤疗效、降低或预防毒副反应作一综述。
[摘要] 近年来研究显示，肠道菌群不仅与肿瘤的发生、发展和转移有关，还可通过参与化疗药物代谢导致化疗相关性肠炎、激活或调控免疫反应及信号通路、促进细胞因子的产生、修复肠道黏膜损伤等多种途径影响肿瘤患者对化疗、放疗和生物治疗的疗效和不良反应。肠道菌群种类繁多、丰度可变，个体差异性是患者对抗肿瘤治疗产生不同反应的原因之一。而肠道菌群受不同外源性因素的影响，故对其干预或重塑将增强抗肿瘤治疗的疗效和减轻治疗相关的毒副作用，改善肿瘤患者的生活质量和预后。本文就肠道菌群对化疗、放疗和免疫治疗的调控作用及相关机制，就靶向肠道菌群的治疗以提高抗肿瘤疗效、降低或预防毒副反应作一综述。
2019, 26(7):817-822.
DOI: 10.3872/j.issn.1007-385X.2019.07.016
Abstract:
[摘要] TEA转录因子4（TEAD4）是Hippo 信号通路中转录共激活子YAP/TAZ下游最重要的转录因子TEAD家族的成员之一。近年来，TEAD4 的促癌作用被逐渐发现，其可与YAP形成转录复合体或不依赖于YAP独立调控下游相关靶基因的表达，在胃肠道肿瘤、肝癌、肺癌、乳腺癌等多种人类实体肿瘤中发挥促癌作用，导致肿瘤的发生和进展，并且是多种肿瘤不良预后的标志。此外，靶向TEAD4 及以阻断YAP-TEAD4 结合为靶点的药物在多种肿瘤的体外实验及动物模型中取得显著的治疗效果，提示TEAD4 可能是肿瘤治疗的一个理想靶点。本文就目前TEAD4 在肿瘤发生、发展及治疗中的研究现状作一总结及展望，以期为TEAD4的后续研究及以其为靶点的肿瘤治疗提供新思路。
[摘要] TEA转录因子4（TEAD4）是Hippo 信号通路中转录共激活子YAP/TAZ下游最重要的转录因子TEAD家族的成员之一。近年来，TEAD4 的促癌作用被逐渐发现，其可与YAP形成转录复合体或不依赖于YAP独立调控下游相关靶基因的表达，在胃肠道肿瘤、肝癌、肺癌、乳腺癌等多种人类实体肿瘤中发挥促癌作用，导致肿瘤的发生和进展，并且是多种肿瘤不良预后的标志。此外，靶向TEAD4 及以阻断YAP-TEAD4 结合为靶点的药物在多种肿瘤的体外实验及动物模型中取得显著的治疗效果，提示TEAD4 可能是肿瘤治疗的一个理想靶点。本文就目前TEAD4 在肿瘤发生、发展及治疗中的研究现状作一总结及展望，以期为TEAD4的后续研究及以其为靶点的肿瘤治疗提供新思路。
2019, 26(7):823-827.
DOI: 10.3872/j.issn.1007-385X.2019.07.017
Abstract:
[摘要] 胰岛素样生长因子（IGF）系统是人体内的一组多肽类物质，其分泌细胞广泛分布在人体各组织中，具有促生长作用。IGF系统能够诱导肿瘤细胞出现EMT，进而增强肿瘤细胞干性、自我更新和转移潜能，向恶性肿瘤发展。研究显示，IGF系统的过表达与胃癌（GC）的发生存在着密切关联，例如IGF-1 和IGF-1R在GC组织中就有着明显表达，其表达水平随着GC从良性到恶性的转变而逐渐増强。近年来研究也表明，在GC细胞癌变的过程中，EMT起着关键性的作用，它使得肿瘤细胞具备了侵袭和迁移能力，而削弱和抑制这种能力则成为了一种有针对性的治疗方法，这其中有着很大的研究空间。临床数据显示，患者化疗前后血清中的IGF-1 表达水平也能够直接反映化疗的效果，这更显示IGF 可作为GC筛查的重要标志物，为GC精准治疗的研究提供可靠依据。上述一系列发现，使得IGF有望成为新的判断肿瘤发生及转移的诊疗指标。
[摘要] 胰岛素样生长因子（IGF）系统是人体内的一组多肽类物质，其分泌细胞广泛分布在人体各组织中，具有促生长作用。IGF系统能够诱导肿瘤细胞出现EMT，进而增强肿瘤细胞干性、自我更新和转移潜能，向恶性肿瘤发展。研究显示，IGF系统的过表达与胃癌（GC）的发生存在着密切关联，例如IGF-1 和IGF-1R在GC组织中就有着明显表达，其表达水平随着GC从良性到恶性的转变而逐渐増强。近年来研究也表明，在GC细胞癌变的过程中，EMT起着关键性的作用，它使得肿瘤细胞具备了侵袭和迁移能力，而削弱和抑制这种能力则成为了一种有针对性的治疗方法，这其中有着很大的研究空间。临床数据显示，患者化疗前后血清中的IGF-1 表达水平也能够直接反映化疗的效果，这更显示IGF 可作为GC筛查的重要标志物，为GC精准治疗的研究提供可靠依据。上述一系列发现，使得IGF有望成为新的判断肿瘤发生及转移的诊疗指标。
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- 《中国肿瘤生物治疗杂志》
- 1994年创刊
- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
- 邮编：200433
- 电话：021-81871002-22
- 电子邮箱：cjcb@biother.cn
- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
- CN 31-1725/R
- 国内定价： ￥20元/册
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.